Insulin antibodies

A number of disorders are associated with the development of insulin resistance. Although some cases are due to autoimmune responses such as the development of anti-insulin or anti-insulin receptor antibodies, insulin resistance often results from defects at the cellular level in the insulin receptor or in postreceptor function. 

Spencer, R. D., Toledo, F. B., Williams, B. T., and Yoss, N. L., Design, construction, and two applications for an automated flow-cell polarization fluorometer with digital read out Enzyme-inhibitor (antitrypsin) assay and antigen-antibody (insulin-insulin antiserum) assay. Clin. Chem. 19, 838-844 (1973). 

Human T-cell lymphotrophic virus Immunoglobulin electrophoresis Insulin antibody Insulin assay... 

Medical and diagnostic products, such as monoclonal antibodies, insulin, interferon, various cell-line stimulating factors, anti-clotting agents, enzyme inhibitors, steroids, antibiotics as well as bacterial and viral vaccines, are manufactured by means of aseptic fermentation from different raw materials by microbial and animal cell cultures. 

Insulin antibodies have been separated by paper electrophoresis from the blood of insulin-treated patients. These antibodies act on insulin labeled with iodine 131, and a cross reaction occurs between the antibodies and insulin obtained from humans, pork, and beef. Insulin antibodies appear in the blood after bovine or foreign insulin administration. The amount of antibody is proportional to the amount of insulin injected. The antibody insulinic complex has little insulinlike activity. Insulin antibody develops in those patients who receive large doses of insulin, and it is therefore impossible to judge whether the insulin resistance results from antibody formation or from the appearance of agents with autoimmune activity. 

Despite the marked conformity in the insulin binding curves of the insulins derived from different species and exposed to one anti-pig-insulin-antiserum, a marked discrepancy between immunological inhibition of biological activity and radio-immunologi-cally measurable insulin was noted. In contrast to the well known incomplete inhibition of the biological activity of serum insulin effected by antibodies, insulin activity in the incubation medium... 

First trials with CD3 antibodies for therapy of autoimmune diseases (insulin-dependent diabetes mellitus psoriatic arthritis... 

An individual can also become insulin resistant because of the development of antibodies gainst insulin. These patients have impaired receptor function and become so unresponsive to insulin that the daily dose requirement may be in excess of500 units per day (U/ d), rather than the usual 40 to 60 U/d. High-potency insulin in a concentrated form (U500 see the Summary Drug Table Insulin Preparations) is used for patients requiring more than 200 U/d. 

Ovarian enlargement, hemoperitoneum, febrile reactions, multiple pregnancies, hypersensitivity Failure to respond to therapy due to development of antibodies, hypothyroidism, insulin resistance, swelling of the joints, joint and/or muscle pain Same as somatropin... 

These hormones cause few adverse reactions when administered as directed. Antibodies to somatropin may develop in a small number of patients, resulting in a failure to experience response to therapy, namely, failure of the drug to produce growth in the child. Some patients may experience hypothyroidism or insulin resistance Swelling, joint pain, and muscle pain may also occur. 

When amphotericin B or diuretics are administered with ACTH, the potential for hypokalemia is increased. There may be an increased need for insulin or oral antidiabetic drag s in the patient with diabetes who is taking ACTH. There is a decreased effect of ACTH when the agent is administered with the barbiturates. Profound muscular depression is possible when ACTH is administered with the anticholinesterase drugp. Live virus vaccines taken while taking ACTH may potentiate virus replication, increase vaccine adverse reaction, and decrease the patient s antibody response to the vaccine... 

The concept of immunoassay was first described in 1945 when Landsteiner suggested that antibodies could bind selectively to small molecules (haptens) when they were conjugated to a larger carrier molecule. This hapten-specific concept was explored by Yalow and Berson in the late 1950s, and resulted in an immunoassay that was applied to insulin monitoring in humans. This pioneering work set the stage for the rapid advancement of immunochemical methods for clinical use. 

Biotechnology era beginning First recombinant DNA products Human insulin Human growth hormone Interferons, etc. Monoclonal antibodies Nucleotide blockage Growth in use of natural products and neutraceuticals... 

Petruzzelli L, Herrera R, Arenas-Garcia R, Fernandez R, Bimbaum MJ, Rosen OM 1986 Isolation of a Drosophila genomic sequence homologous to the kinase domain of the human insulin receptor and detection of the phosphorylated Drosophila receptor with an anti-peptide antibody. Proc Natl Acad Sci USA 83 4710-4714 Podskalny J, McElduff A, Gorden P 1984 Insulin receptors on Chinese hamster ovary (CHO) cells altered insulin binding to glycosylation mutants. Biochem Biophys Res Commun 125 70-75... 

Using this approach, EGF has been successfully conjugated by disulfide exchange to the A chain of diphtheria toxin (Shimisu et al., 1980). A cystaminyl derivative of insulin also could be conjugated to the A chain of diphtheria toxin by this method (Miskimins and Shimizu, 1979). Other references to disulfide exchange using cystamine include Oeltmann and Forbes (1981) and Bacha et al. (1983) who prepared antibody-toxin and peptide-toxin conjugates, respectively. 

After the approval of the first product, recombinant insulin, in 1982, progress in the development of new recombinant protein pharmaceuticals was slow ([10], Fig. 17.1). The number of biotechnology-derived drugs and vaccines approved by the US Food and Dmg Administration (FDA) has increased significantly only since 1995. More recently, sales of biologies have skyrocketed, e.g. from 900 million in 1999 to an estimated 3.5 billion in 2001 for monoclonal antibodies [11]. The annual global market for biopharmaceuticals is estimated to have increased from 12 billion US to 30 billion US in 2003 [12]. 500 candidate biopharmaceuticals are undergoing clinical evaluation and over one hundred protein-based therapeutics are in the... 

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